Download Syed_ARTSS Final Presentation3

By Husham Syed-Mohammed
Richard Grucza, Andrew Plunk, Laura Bierut, Pamela Hipp
• GGT is a glycoprotein enzyme involved in
counteracting oxidative stress
• Increase in serum levels with repeated excessive
alcohol consumption
• Asparate and Alanine Aminotransferase are liver
enzymes involved in amino acid metabolism.
• Used clinically as indicators of liver cell injury
• Commonly tested in clinical settings in liver panel
tests
• Studies have linked high GGT levels in risk
prediction of type 2 diabetes, cardiovascular
events, chronic kidney disease, and cancer
• Numerous studies have associated GGT with
all-cause mortality independent of alcohol use
• Is GGT a more sensitive indicator of alcohol
drinking patterns than ALT or AST?
• Do drinking patterns impact GGT levels over
and above total alcohol intake?
• How are alcohol drinking behaviors associated
with all-cause mortality?
• How does GGT influence mortality at different
levels of drinking?
• National Health and Nutritional
Examination Survey
• Designed to assess the health
and nutritional status of adults
and children in the United States
• Began in early 1960’s and data is
still being currently collected
• Combines interviews, physical
examinations, and lab tests
• N=16,811
• Data from five administrations of NHANES
(1999-2008)
• All past-year drinkers 21 years and older
• Drinkers were described as those having at
least 12 drinks in the past year
• Whites, Hispanics, and Blacks
• Compared the association of binge-drinking
and non binge-drinking behaviors with GGT,
AST, and ALT serum levels
• Binge-drinking was described as having five or
more drinks per drinking episode
• “Moderate-drinking” was described as having
four or less drinks per drinking episode
GGT is More Sensitive to Binge-Drinking and ModerateDrinking Patterns
Regression Coefficient
2.5000
GGT
AST
ALT
Binge Drinking Days Per
Week
2.0000
1.5000
1.0000
Moderate Drinking Days
per Week
0.5000
0.0000
Male
Female
Male
Female
Male
Liver Enzyme (Enzyme levels analyzed as T-Scores)
FIGURE 1. Analysis were controlled for age, smoking behaviors, race, and weight to height ratio.
Female
• Compared association of serum GGT levels
with different drinking patterns in different
categories of total alcohol consumption
• This was to test our hypothesis if drinking
patterns impact GGT levels over and above
total alcohol intake?
Total Alcohol Consumption and Binge Drinking Increase GGT Levels
59
58
Serum GGT Levels (T-Score)
57
56
Average Weekly
Consumption of
Alcohol
55
54
0-2 drinks per week
2-6 drinks per week
53
6-14 drinks per week
14-192 drinks per week
52
51
50
Zero
Light
Med.
Heavy
Binge-Drinking Behavior
FIGURE 2. Zero=zero days in year binge drinking, light=1-12 days in year binge drinking, med=13-52 days in year binge-drinking, heavy=53 or more days
in year binge drinking.
• N=6,834
• Used the same inclusion criteria as previous
study
• Survival Analysis: Mortality predicted from
alcohol drinking patterns
• Survival Analysis: Mortality predicted from
GGT serum levels in different binge-drinking
categories
Effects of Drinking Patterns on Mortality
1.3
1.2
Hazard Ratio
1.1
1
Male Hazard Ratios
0.9
0.8
Female Hazard Ratios
0.7
Moderate Drinks Per Week
Binge Drinks Per Week
Categories
Figure 3. Controls for this analysis included age, race, smoking behavior, poverty index, and waist to hip ratio.
GGT is More Predictive of Mortality in Heavy Binge-Drinkers
1.6
1.5
Hazard Ratio
1.4
1.3
Male Hazard Ratios
1.2
Female Hazard Ratios
1.1
1
0 Days in Year Binge Drinking
1-12 Days in Year Binge Drinking
13-52 Days in Year Binge Drinking
Binge Drinking Category
Figure 4 The analysis was controlled for age, race, smoking behavior, poverty index, and waist to hip ratio.
• GGT serum levels are the most sensitive liver
enzyme associated with alcohol consumption
• Both the amount of drinking and the pattern
of drinking effects GGT levels
• Binge-drinking behaviors strongly predict
mortality, while moderate-drinking behaviors
do not seem to have an effect
• The association between GGT and mortality
may be stronger in heavier drinkers
• Thank you everyone who helped with the
research this summer:
– ARTSS Internship program
– Richard Grucza
– Pamela Hipp
– Andrew Plunk
– Laura Bierut